The proposed research concerns an anorexigenic substance present in the urine of animals and man. This substance, termed FMS 1A in conformity with its relationship to fat-mobilizingsubstance, will be extracted from rat and human urine by precipitation with ethanol-benzoic acid in the cold at pH 5.3. An active fraction has been obtained by gel filtration on Sephadex G-75 which possesses specific activity 10 times greater than that of FMS 1A. This fraction will be chromatographed on DEAE-cellulose, hydroxy apatite and other media, and rechromatographed under varied conditions in an attempt to achieve greater purity. A further active preparation of high activity has been obtained from the urine of hypophysectomized rats. This preparation and human anorexigenic substance will also be purified by the same methods. Attempts at preliminary characterization of these materials will utilize amino acid-specific proteolytic enzymes and pronase to attack peptide bonds, and disulfide agents to attack S-S bonds of the active or carrier peptide or protein material. Dansyl chloride and 2,4 dinitrofluorobenzene will be employed for end-group analysis. Nutritional studies will be aimed at learning the effects of dietary proportions of protein, fat and carbohydrate upon excretion of anorexigenic substance by rats, the effects of long-term administration of this material, and the possibility of "escape" from its effects. Physiological studies will focus on the specificity of its appetite-depressing activity, especially its effects upon blood pressure, production of hormone releasing factors and other functions mediated by the hypothalamus. If sufficient purification can be achieved, radioimmunoassay of the material will be attempted and utilized for investigation of its site of origin and its distribution.